Obesity is a risk factor of diseases such as diabetes mellitus, hypertonia, and heart disease, which threaten health of people in advanced countries. Obesity means physical conditions wherein adipose tissues have abnormally accumulated. Adipose tissues are special organs wherein surplus in vivo energies are stored as fat or triglyceride, and constructed of fibroblasts including adipocytes and their precursors, macrophages, blood vessel surrounding cells, blood cells, and the like.
Adipocytes are said to amount from ⅓ to ⅔ of cells which are present in adipose tissues and to accumulate fats or triglycerides therein. Adipocytes differentiate and mature through the process starting from mesenchymal multipotent stem cells, and growing into lipoblasts which have acquired a base as adipocytes, precursor adipocytes with no lipid droplets but having initial markers of adipocytes, immatured adipocytes containing lipid droplets, and finally into matured adipocytes containing a large quantity of accumulated fats. Adipocytes of adults suffering from slight obesity hypertrophically grow due to increase in the amount of accumulated triglyceride. Number of adipocytes increases as the degree of obesity becomes conspicuous. Therefore, decreasing the number of adipocytes by controlling differentiation and maturation or suppressing hypertrophia of matured adipocytes are expected to stop progress of obesity by suppressing the increase in the amount of accumulated fats, and to treat obesity. Control of in vivo adipocyte differentiation has been proven to undergo either positively or negatively according to a number of factors derived from environmental factors such as ingestion, exercise, and so on. As cytokines which control differentiation of adipocytes from adipocyte precursors, tumor necrosis factor-α (TNF-α: Torti F. M. et al., Science, Vol. 229, p 867 (1985)), transforming growth factory-β (Ignotz R. A. et al., Proc. Natl. Acad. Sci. USA, Vol. 82, p 8530 (1985)), preadipocyte factor-1 (Pref-1: Smas C. M. et al., Cell, Vol. 73, p 725 (1993)), and the like have been reported. In addition, leptin, the translational product of an ob gene which has recently been cloned, has been reported to possibly decrease the intake amount and the weight of adipose tissues via central nerve system (Levin N. et al. Proc. Natl. Acad. Sci. USA, Vol. 93. P 1726, 1996).
Furthermore, intracerebral peptide-neuropeptide Y which exhibits a strong appetite stimulating effect and its receptor are gathering attention as materials for the development of an obesity suppressing pharmaceutical (Sainsburg A. et al, Diabetologia, Vol. 39, p 353, 1996). These cytokines are expected to become a therapeutic agent for obesity due to their adipocyte depressing action on accumulation of fat. Clinical tests as an obesity therapeutic or preventive agent is ongoing on some of these cytokines such as leptin.
At present, one obesity therapeutic or preventive agent is commercially available in the USA under the Redux™ (American Home Products Co.). Other drugs such as Meridia (Kunol Co.) and Xenical (Roche Co.) will be approved as an obesity treating agent or a fat absorption inhibitor in the USA. The treatments method using these pharmaceuticals, however, are not necessarily satisfactory in the effects and therapeutic results. Development of a new agent which is available exhibits for these pharmaceuticals higher curative effect and less side effect usable have been desired.